We propose to fully characterize physicochemically bile salt-lecithin and bile salt-lecithin-cholesterol micellar solutions in terms of critical micellar concentrations and size and shape of micelles, and compare this information with the properties of the micelles in native gallbladder and hepatic bile. Employing ultrafiltration and quasielastic light scattering spectroscopy we intend to study these micellar solutions as a function of total lipid concentration, lipid composition, neutral electrolyte concentration, and temperature. We will also study by quasielastic light scattering spectroscopy, the characteristics of bile salt micellar systems supersaturated with cholesterol, and measure growth kinetics during the nucleation and precipitation of the excess cholesterol. We plan to study the self aggregation of free and conjugated bilirubin as a function of pH, dye concentration, added neutral electrolyte and the presence of bile micelles by a combination of surface tension, uv-vis spectrophotometry and quasielastic light scattering spectroscopy. In addition, we will measure the precipitation and growth of solid Calcium bilirubinate from model and native bile systems by manipulating pH and CaCl2 concentration. We will continue our studies on chlorpromazine induced bile secretory failure in the Rhesus monkey. We plan to couple pharmaco-physiological experiments on bile flow and biliary lipid secretion with morphological studies of liver biopsies from monkeys using freeze fracture and transmission electron microscopy and autoradiography during chlorpromazine hydrochloride induced cholestasis. BIBLIOGRAPHIC REFERENCES: Lester, R., Carey, M.C., Little, J.M., Cooperstein, L.A. and Dowd, S.R.: Crustacean intestinal detergent promotes sterol solubilization. Science 189:1098-1100, 1975. Carey, M.C., Montet, J.C. and Small, D.M.: Surface and solution properties of steroid antibiotics, 3-acetoxyl fusidic acid, cephalosporin P1 and helvolic acid. Biochemistry 14:4895-4905, 1975.